A combined human gastruloid model of cardiogenesis and neurogenesis

• Published in: iScience Vol. 25; no. 6; p. 104486
• Main Authors: Olmsted, Zachary T., Paluh, Janet L.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 17-06-2022; Elsevier
• Subjects: Cell biology; Genomics; Stem cells research; Cell biology; Genomics; Stem cells research
• ISSN: 2589-0042; 2589-0042
• DOI: 10.1016/j.isci.2022.104486

Multi-lineage development from gastruloids is enabling unprecedented opportunities to model and study human embryonic processes and is expected to accelerate ex vivo strategies in organ development. Reproducing human cardiogenesis with neurogenesis in a multi-lineage context remains challenging, requiring spatiotemporal input of paracrine and mechanical cues. Here we extend elongating multi-lineage organized (EMLO) gastruloids to include cardiogenesis (EMLOC) and describe interconnected neuro-cardiac lineages in a single gastruloid model. Contractile EMLOCs recapitulate numerous interlinked developmental features including heart tube formation and specialization, cardiomyocyte differentiation and remodeling phases, epicardium, ventricular wall morphogenesis, chamber-like structures and formation of a putative outflow tract. The EMLOC cardiac region, which originates anterior to gut tube primordium, is progressively populated by neurons in a spatial pattern mirroring the known distribution of neurons in the innervated human heart. This human EMLOC model represents a multi-lineage advancement for the study of coincident neurogenesis and cardiogenesis.
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•A trunk-biased microenvironment primed for cardiogenesis•Gastruloid-derived spatiotemporal features of cardiogenesis•Neurogenesis coupled with neuronal population of cardiac regions•Neuro-cardiac multi-lineage, multi-tissue linked developmental model
Cell biology; Stem cell research; Genomics